Angiogenesis inhibition, targeting vascular endothelial growth factor (VEGF) or its receptors, is an established treatment for solid tumors. A common side effect of this treatment is the development of sometimes severe hypertension. This hypertension is associated with a decrease in nitric oxide production, activation of the endothelin-signaling pathway and renin suppression. The mechanism underlying activation of the endothelin-signaling pathway is not fully understood. Both activation of endothelial cells and disinhibition of the VEGF-induced suppression of endothelin production by endothelial cells may be involved. The development of hypertension can be a reason to discontinue the angiogenesis inhibitor, thereby compromising anticancer treatment, but possibly is also a biomarker for a favorable antitumor response.